OVERALL DESCRIPTION: This program project proposal continues to be focused on determination of the sites and mechanisms of action of volatile anesthetics. The current applications proposes four research projects and three cores. Three of the projects continue studies begun by investigators in the previous funding period, and one investigator is new to the program project. The projects are interrelated by the application of a common test panel of compounds of standard anesthetic potency which includes non-immobilizer and translational compounds that were used in the previous funding period. A new feature is the introduction of mutagenesis of putative anesthetic active sites on membrane receptors and studies utilizing transgenic mouse technology. The program will continue to have biannual meetings involving the participant investigators and a number of consultants and advisory board members.